Publications by authors named "Zongxiang Tang"

81 Publications

Paeoniflorin alleviates CFA-induced inflammatory pain by inhibiting TRPV1 and succinate/SUCNR1-HIF-1α/NLPR3 pathway.

Int Immunopharmacol 2021 Nov 26:108364. Epub 2021 Nov 26.

Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China; Department of Neurology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China. Electronic address:

Background: Treatment of chronic inflammatory pain remains a major goal in the clinic. It is thus of prime importance to characterize inherent pathophysiological pathways to design new therapeutic strategies and analgesics for pain management. Paeoniflorin (PF), a monoterpenoid glycoside from Paeonia lactiflora Pallas plants, possesses promising anti-nociceptive property. However, therapeutic effect and underlying mechanism of action of PF on inflammatory pain have not yet been fully elucidated. In this study, we aim to investigate the analgesic effect further and clarify its mechanism of action of PF on complete freund's adjuvant (CFA)-evoked inflammatory pain.

Methods: Twenty-four male mice were divided into 3 groups: sham, CFA, and CFA + PF groups (n = 8/group). Mice were treated with normal saline or PF (30 mg/kg) for 11 days. Footpad swelling (n = 8/group), mechanical (n = 8/group) and thermal hypersensitivity (n = 8/group) were measured to evaluate the analgesic effect of PF on CFA-injected mice. At the end of the animal experiment, blood and L4-L6 dorsal root ganglion neurons were collected to assess the therapeutic effect of PF on CFA-induced inflammatory pain. Next, hematoxylin and eosin, quantitative realtime PCR, ELISA, capsaicin and dimethyl succinate induced pain test (n = 8/group), motor coordination test (n = 8/group), tail flicking test (n = 8/group), pyruvate and succinate dehydrogenase assay (n = 6/group), immunohistochemical staining, were performed to clarify the action mechanism of PF on CFA-evoked inflammatory pain. Besides, the effect of PF on TRPV1 was evaluated by whole-cell patch clamp recording on primary neurons (n = 7). Finally, molecular docking further performed to evaluate the binding ability of PF to TRPV1.

Results: PF significantly relieved inflammatory pain (P < 0.001) and paw edema (P < 0.001) on a complete Freund adjuvant (CFA)-induced peripheral inflammatory pain model. Furthermore, PF inhibited neutrophil infiltration (P < 0.01), IL-1β increase (P < 0.01), and pain-related peptide substance P release (P < 0.001). Intriguingly, CFA-induced succinate aggregation was notably reversed by PF via modulating pyruvate and SDH activity (P < 0.01). In addition, PF dampened the high expression of subsequent succinate receptor SUCNR1 (P < 0.01), HIF-1α (P < 0.05), as well as the activation of NLPR3 inflammasome (P < 0.05) and TRPV1 (P < 0.05). More importantly, both capsaicin and dimethyl succinate supplementation obviously counteracted the pain-relieving effect of PF and TRPV1 (P < 0.01 or P < 0.001).

Conclusion: Our findings suggest that PF can significantly relieve CFA-induced paw swelling, as well as mechanical and thermal hyperalgesia. PF alleviated inflammatory pain partly through inhibiting the activation of TRPV1 and succinate/SUCNR1-HIF-1α/NLPR3 pathway. Furthermore, we found that PF exerted its analgesic effect without affecting motor coordination and pain-related cold ion-channels. In summary, this study may provide valuable evidence for the potential application of PF as therapeutic strategy for inflammatory pain treatment.
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http://dx.doi.org/10.1016/j.intimp.2021.108364DOI Listing
November 2021

Desensitization of TRPV1 Involved in the Antipruritic Effect of Osthole on Histamine-Induced Scratching Behavior in Mice.

Evid Based Complement Alternat Med 2021 13;2021:4012812. Epub 2021 Oct 13.

College of Basic Medicine, Guangxi University of Chinese Medicine, Nanning 530299, China.

Osthole has been isolated from the fruits of (L.) Cusson, which has been used in Chinese traditional medicine to treat pruritic disorders for a long time. However, the antipruritic mechanism of osthole is not fully understood. In the present study, using calcium imaging, molecular docking, and animal scratching behavior, we analyzed the pharmacological effects of osthole on transient receptor potential vanilloid 1 (TRPV1). The results showed that osthole significantly induced calcium influx in a dose-dependent manner in dorsal root ganglion (DRG) neurons. Osthole-induced calcium influx was inhibited by AMG9810, an antagonist of TRPV1. Osthole and the TRPV1 agonist capsaicin-induced calcium influx were desensitized by pretreatment with osthole. Furthermore, molecular docking results showed that osthole could bind to TRPV1 with a hydrogen bond by anchoring to the amino acid residue ARG557 in the binding pocket of TRPV1. In addition, TRPV1 is a downstream ion channel for the histamine H1 and H4 receptors to transmit itch signals. Osthole attenuated scratching behavior induced by histamine, HTMT (histamine H1 receptor agonist), and VUF8430 (histamine H4 receptor agonist) in mice. These results suggest that osthole inhibition of histamine-dependent itch may be due to the activation and subsequent desensitization of TRPV1 in DRG neurons.
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http://dx.doi.org/10.1155/2021/4012812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8528571PMC
October 2021

Mas-related G protein-coupled receptor D is involved in modulation of murine gastrointestinal motility.

Exp Physiol 2021 Dec 3;106(12):2502-2516. Epub 2021 Nov 3.

Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu, PR China.

New Findings: What is the central question of this study? The physiological function of Mas-related G protein-coupled receptor D (MrgprD) in gastrointestinal motility is unknown. The aim of this study was to assess the effects of MrgprD and its receptor agonists on murine gastrointestinal motility. What is the main finding and its importance? Mrgprd deficiency improved murine gastrointestinal motility in vivo but had no effects on the spontaneous contractions of murine intestinal rings ex vivo. Systemic administration of the MrgprD ligand, either β-alanine or alamandine, delayed gastrointestinal transit in vivo and attenuated the spontaneous contractions of isolated intestinal rings ex vivo.

Abstract: Mas-related G protein-coupled receptor D (MrgprD) was first identified in sensory neurons of mouse dorsal root ganglion and has been demonstrated to be involved in sensations of pain and itch. Although expression of MrgprD has recently been found in the gastrointestinal (GI) tract, its physiological role in GI motility is unknown. To address this question, we used Mrgprd knockout (Mrgprd ) mice and MrgprD agonists to examine the effects of Mrgprd gene deletion and MrgprD signalling activation, respectively, on murine intestinal motility, both in vivo and ex vivo. We observed that the deletion of Mrgprd accelerated the transmission of charcoal through the mouse GI tract. But Mrgprd deficiency did not affect the mean amplitudes and frequencies of spontaneous contractions in ileum ex vivo. Colonic motor complexes in the proximal and the distal colon were recorded from wild-type and Mrgprd mice, but their control frequencies were not different. Moreover, in wild-type mice, systemic administration of an MrgprD agonist, either β-alanine or alamandine, delayed GI transit in vivo and suppressed spontaneous contractions in the ileum and colonic motor complexes in the colon ex vivo. Our results suggest that MrgprD and its agonist are involved in the modulation of GI motility in mice.
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http://dx.doi.org/10.1113/EP089958DOI Listing
December 2021

Beneficial Effects of Quercetin on Microcystin-LR Induced Tight Junction Defects.

Front Pharmacol 2021 10;12:733993. Epub 2021 Sep 10.

Department of Physiology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China.

Quercetin has numerous functions including antioxidant and anti-inflammatory effects. The beneficial effect of quercetin against microcystin-LR (MC-LR)-induced testicular tight junctions (TJs) defects and were investigated. Significant reductions in transepithelial electrical resistance, occludin, and zonula occludens-1(ZO-1) levels were detected in the MC-LR-treated TM4 cells, and quercetin attenuated these effects. Interestingly, quercetin suppressed MC-LR-induced phosphorylation of protein kinase B (AKT). It effectively inhibited the accumulation of reactive oxygen species (ROS) in cells stimulated by MC-LR. In addition, ROS inhibitors blocked the TJ damage that is dependent on the AKT signaling pathway induced by MC-LR. In conclusion, our results suggest that alleviates MC-LR-impaired TJs by suppressing the ROS-regulated activation of the AKT pathway.
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http://dx.doi.org/10.3389/fphar.2021.733993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8462518PMC
September 2021

A Buthus martensii Karsch scorpion sting targets Nav1.7 in mice and mimics a phenotype of human chronic pain.

Pain 2021 Jul 8. Epub 2021 Jul 8.

Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210028, China. School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China. Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 065140, USA. Department of Pharmacology and Chemical Biology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Shimadzu Biomedical Research Laboratory, Shanghai 200233, China. School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China. The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, China. Bio-Signal Technologies, LLC, Anchorage, AK 99508, USA. Department of Neurology and Rehabilitation Research Center, Veterans Affairs, Connecticut Healthcare System, West Haven, CT 06516, USA.

Gain: and loss-of-function mutations in Nav1.7 cause chronic pain and pain insensitivity, respectively. The preferential expression of Nav1.7 in peripheral nervous system and its role in human pain signaling make Nav1.7 a promising target for next-generation pain therapeutics. However, pharmacological agents have not fully recapitulated these pain phenotypes, and, due to the lack of subtype-selective molecular modulators, the role of Nav1.7 in the perception of pain remains poorly understood. Scorpion venom is an excellent source of bioactive peptides that modulate various ion channels, including voltage-gated sodium (Nav) channels . Here, we demonstrate that Buthus martensii Karsch scorpion venom (BV) elicits pain responses in mice through direct enhancement of Nav1.7 activity, and have identified that Makatoxin-3, an α-like toxin as a critical component for BV-mediated effects on Nav1.7. Blocking other Nav subtypes did not eliminate BV-evoked pain responses, supporting the pivotal role of Nav1.7 in BV-induced pain . Makatoxin-3 acts on the S3-S4 loop of voltage sensor domain IV (VSD4) of Nav1.7, which causes a hyperpolarizing shift in the steady-state fast inactivation and impairs inactivation kinetics. We also determined the key residues and structure-function relationships for the toxin-channel interactions, which are distinct from those of other well-studied α-toxins. This study not only reveals a new mechanism underlying BV-evoked pain, but also enriches our knowledge of key structural elements of scorpion toxins that are pivotal for toxin-Nav1.7 interaction, which facilitates the design of novel Nav1.7 selective modulators.
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http://dx.doi.org/10.1097/j.pain.0000000000002397DOI Listing
July 2021

P2X7R in Mast Cells is a Potential Target for Salicylic Acid and Aspirin in Treatment of Inflammatory Pain.

J Inflamm Res 2021 2;14:2913-2931. Epub 2021 Jul 2.

School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People's Republic of China.

Background: Mast cells are well known for their role in inflammatory pain. P2X7 receptor (P2X7R) has attracted much attention due to its prominent role in inflammatory diseases. Salicylates are commonly used anti-inflammatory and analgesic drugs. Until now, little has been known about whether P2X7R in mast cells is involved in inflammatory pain and whether it is a potential target for salicylates.

Methods: First, the expression of P2X receptors in mouse peritoneal mast cells was detected by using RT-PCR, immunofluorescence, calcium imaging and electrophysiological technique. In addition, the functions of P2X receptors, especially P2X7R, in mast cells were studied by using QPCR, ELISA and behavioral tests. Furthermore, P2X7R was used as a target to screen for some anti-inflammatory monomers that could inhibit its activity. At last, the effect of salicylic acid (SA) and aspirin (ASA) on the activity of P2X7R was studied by using calcium imaging, electrophysiological technique, ELISA, real-time PCR, behavioral tests, immunofluorescence and molecular docking.

Results: We found that P2X1, P2X3, P2X4 and P2X7 receptors were expressed in mouse peritoneal mast cells. The functions of different P2X receptors were various. Activation of P2X7R in mouse mast cells induced the release of inflammatory mediators, such as histamine, IL-1β, and CCL3. In addition, inflammation pain induced by high concentrations of ATP could be alleviated by P2X7R blockers or mast cell defects. Interestingly, SA or ASA could reduce high concentrations of ATP-induced inward current, P2X7R upregulation, mediators release, and inflammatory pain. SA or ASA also inhibited the inward current evoked by P2X7R agonist, BZATP. Molecular docking showed that SA or ASA had affinity for the cytoplasmic GDP-binding region of P2X7R.

Conclusion: P2X7R in mast cells was involved in inflammation pain by releasing inflammatory mediators, and P2X7R might be a potential target for SA and ASA analgesia.
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http://dx.doi.org/10.2147/JIR.S313348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259951PMC
July 2021

Assessing the post-treatment therapeutic effect of pinaverium in irritable bowel syndrome: a randomized controlled trial.

Sci Rep 2021 07 6;11(1):13894. Epub 2021 Jul 6.

The Macrohard Institute of Health, 231 North Ave., Battle Creek, MI, 49017, USA.

Irritable bowel syndrome (IBS) is the most common gastrointestinal disorder significantly decreasing patients' lives of quality and placing huge economic burden on our society. Existing studies indicated that the therapeutic effects maintained for a period of time after the treatments were discontinued. It is clinically important to assess these post-treatment therapeutic effects (PTTE), which prevent IBS from relapsing. To assess the PTTE in pinaverium treatment and obtain high-quality evidence to justify the use of PTTE for long-term IBS management, we performed this controlled, double blind study on patients with IBS who were randomized to pinaverium 50 mg (n = 132) or placebo (n = 132), three times daily, for 4 weeks, and were followed up for 57 weeks after the treatments. The primary endpoints were abdominal pain and stool consistency. The secondary endpoints were pain frequency and stool frequency. The tertiary endpoints were global overall symptom and adverse events. Three days after pinaverium was discontinued, endpoints rebounded only 23.2-42.8% (P < 0.015 cf. placebo). The PTTE (P < 0.05 cf. placebo) lasted 9-17 weeks, which is similar to other antispasmodics with a 15-week treatment in striking contrast to ≥ 1 year PTTE in cognitive behavior therapy and < 1 week PTTE in serotonin antagonist treatment indicating that PTTE length markedly depends on the medication class used for the treatment and less depends on treatment length. After 17 weeks, the stage could be considered as an IBS natural history [no significant differences between pinaverium and placebo (all endpoints' P's > 0.05)], during which an average of 51.5-56.4% of patients (pool pinaverium and placebo data together) had IBS symptoms. These results provide clinical insights into efficient and cost-effective management of refractory IBS, and lend support to the IBS management that the selection of a therapy should consider both its effectiveness during treatment and its PTTE after the treatment.Trial registration number: NCT02330029 (16/08/2016).
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http://dx.doi.org/10.1038/s41598-021-92990-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260803PMC
July 2021

Cimifugin relieves pruritus in psoriasis by inhibiting TRPV4.

Cell Calcium 2021 May 25;97:102429. Epub 2021 May 25.

School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023 China. Electronic address:

Psoriasis is an immune-mediated chronic inflammatory skin disease characterized by erythema, scales, and infiltration of the skin, which causes deleterious effects on patient quality of life. TRP channel played important roles in the generation and conductance of itch signal . According to our results, psoriasis induced itch was TRPV4 dependent, and TRPV4 expression in both epidermis and DRG were up-regulated in psoriasis. Thus, TRPV4 is an attractive candidate for treating psoriasis induced itch. Cimifugin is a common compound in antipruritic Chinese medicine. In our study, GSK1016790A, a TRPV4 channel specific agonist, induced acute itch was inhibited by cimifugin in a dose-dependent manner. Furthermore, cimifugin treatment reduced the scratching behavior and reversed the TRPV4 up-regulation induced by psoriasis. In particular, cimifugin decreased GSK1016790A induced calcium response both in HaCaT cells and DRG neurons. Importantly, in TRPV4 transfected HEK293 cells, GSK101 induced calcium response was also significantly inhibited by cimifugin pretreatment. Consistent with our calcium imaging result, cimifugin pretreatment also inhibited GSK101 induced inward currents. Our study delineated a new role of TRPV4 in psoriasis and emphasized the antipruritic effect of cimifugin, which opened a new avenue to itch management in psoriasis.
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http://dx.doi.org/10.1016/j.ceca.2021.102429DOI Listing
May 2021

FISH landmarks reflecting meiotic recombination and structural alterations of chromosomes in wheat (Triticum aestivum L.).

BMC Plant Biol 2021 Apr 6;21(1):167. Epub 2021 Apr 6.

College of Agronomy, Sichuan Agricultural University, Wenjiang, 611130, Sichuan, China.

Background: DNA sequence composition affects meiotic recombination. However, the correlation between tandem repeat composition and meiotic recombination in common wheat (Triticum aestivum L.) is unclear.

Results: Non-denaturing fluorescent in situ hybridization (ND-FISH) with oligonucleotide (oligo) probes derived from tandem repeats and single-copy FISH were used to investigate recombination in three kinds of the long arm of wheat 5A chromosome (5AL). 5AL arm carries the tandem repeats pTa-535, Oligo-18, and pTa-275, 5AL arm carries the tandem repeats pSc119.2, Oligo-18 and pTa-275, and 5AL arm carries the tandem repeats pSc119.2. In the progeny of 5AL × 5AL, double recombination occurred between pSc119.2 and pTa-535 clusters (119-535 interval), and between pTa-535 and Oligo-18/pTa-275 clusters (535-18 interval). The recombination rate in the 119-535 interval in the progeny of 5AL × 5AL was higher than that in the progeny of 5AL × 5AL. Recombination in the 119-535 interval produced 5AL segments with pTa-535 and pSc119.2 tandem repeats and 5AL segments without these repeats. The 5AL and 5AL segments were localized between the signal sites of the single-copy probes SC5A-479 and SC5A-527. The segment between SC5A-479 and SC5A-527 in the metaphase 5AL was significantly longer than that in the metaphase 5AL.

Conclusion: The structural variations caused by tandem repeats might be one of the factors affecting meiotic recombination in wheat. Meiotic recombination aggregated two kinds of tandemly repeated clusters into the same chromosome, making the metaphase chromosome more condensed. To conclude, our study provides a robust tool to measure meiotic recombination and select parents for wheat breeding programs.
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http://dx.doi.org/10.1186/s12870-021-02947-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025513PMC
April 2021

Comparative Study on Different Skin Pruritus Mouse Models.

Front Med (Lausanne) 2021 23;8:630237. Epub 2021 Feb 23.

School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China.

The animal model is an important tool to study the mechanism of disease formation. Different animal models of pruritus have been adopted based on the purpose of researchers in the study of the itching mechanism. Although the symptoms of various models are quite different, scratching behavior is a key indicator. Therefore, it is necessary to find an animal model that can quickly induce animal scratching and maintain the stability of scratching behavior. In this study, we compared animal models of pruritus induced by four substances and found that the scratching behavior of mice induced by urushiol not only reached the plateau stage quickly but also showed more stability in the plateau phase than that induced by 2,4-dinitrofluorobenzene, oxazolone, and imiquimod. Meanwhile, in the animal model induced by urushiol, the changes of epidermal thickening and inflammatory cell aggregation were also more obvious. In addition, pruritus induced by urushiol is prevalent all over the world, especially in the United States and Europe, involving outdoor groups such as firefighters, forest loggers, and farmers. Therefore, we believe that the urushiol-induced animal model is an ideal choice for the study of the itch formation mechanism and the development of antipruritic drugs.
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http://dx.doi.org/10.3389/fmed.2021.630237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940346PMC
February 2021

Characterization of a new gene for resistance to wheat powdery mildew on chromosome 1RL of wild rye Secale sylvestre.

Theor Appl Genet 2021 Mar 2;134(3):887-896. Epub 2021 Jan 2.

School of Environment, Jiangsu University, Zhenjiang, 212013, China.

Key Message: PmSESY, a new wheat powdery mildew resistance gene was characterized and genetically mapped to the terminal region of chromosome 1RL of wild rye Secale sylvestre. The genus Secale is an important resource for wheat improvement. The Secale species are usually considered as non-adapted hosts of Blumeria graminis f. sp. tritici (Bgt) that causes wheat powdery mildew. However, as a wild species of cultivated rye, S. sylvestre is rarely studied. Here, we reported that 25 S. sylvestre accessions were susceptible to isolate BgtYZ01, whereas the other five confer effective resistance to all the tested isolates of Bgt. A population was then constructed by crossing the resistant accession SESY-01 with the susceptible accession SESY-11. Genetic analysis showed that the resistance in SESY-01 was controlled by a single dominant gene, temporarily designated as PmSESY. Subsequently, combining bulked segregant RNA-Seq (BSR-Seq) analysis with molecular analysis, PmSESY was mapped into a 1.88 cM genetic interval in the terminus of the long arm of 1R, which was closely flanked by markers Xss06 and Xss09 with genetic distances of 0.87 cM and 1.01 cM, respectively. Comparative mapping demonstrated that the corresponding physical region of the PmSESY locus was about 3.81 Mb in rye cv. Lo7 genome, where 30 disease resistance-related genes were annotated, including five NLR-type disease resistance genes, three kinase family protein genes, three leucine-rich repeat receptor-like protein kinase genes and so on. This study gives a new insight into S. sylvestre that shows divergence in response to Bgt and reports a new powdery mildew resistance gene that has potential to be used for resistance improvement in wheat.
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http://dx.doi.org/10.1007/s00122-020-03739-1DOI Listing
March 2021

Antiallergic drug desloratadine as a selective antagonist of 5HT receptor ameliorates pathology of Alzheimer's disease model mice by improving microglial dysfunction.

Aging Cell 2021 01 24;20(1):e13286. Epub 2020 Dec 24.

Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica and State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing, China.

Alzheimer's disease (AD) is a progressively neurodegenerative disease characterized by cognitive deficits and alteration of personality and behavior. As yet, there is no efficient treatment for AD. 5HT receptor (5HT R) is a subtype of 5HT receptor belonging to the serotonin receptor family, and its antagonists have been clinically used as antipsychotics to relieve psychopathy. Here, we discovered that clinically first-line antiallergic drug desloratadine (DLT) functioned as a selective antagonist of 5HT R and efficiently ameliorated pathology of APP/PS1 mice. The underlying mechanism has been intensively investigated by assay against APP/PS1 mice with selective 5HT R knockdown in the brain treated by adeno-associated virus (AAV)-ePHP-si-5HT R. DLT reduced amyloid plaque deposition by promoting microglial Aβ phagocytosis and degradation, and ameliorated innate immune response by polarizing microglia to an anti-inflammatory phenotype. It stimulated autophagy process and repressed neuroinflammation through 5HT R/cAMP/PKA/CREB/Sirt1 pathway, and activated glucocorticoid receptor (GR) nuclear translocation to upregulate the transcriptions of phagocytic receptors TLR2 and TLR4 in response to microglial phagocytosis stimulation. Together, our work has highly supported that 5HT R antagonism might be a promising therapeutic strategy for AD and highlighted the potential of DLT in the treatment of this disease.
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http://dx.doi.org/10.1111/acel.13286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811850PMC
January 2021

Mas-related G protein-coupled receptor D participates in inflammatory pain by promoting NF-κB activation through interaction with TAK1 and IKK complex.

Cell Signal 2020 12 18;76:109813. Epub 2020 Oct 18.

Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.

Mas-related G protein-coupled receptor D (MrgprD) is mainly expressed in small-diameter sensory neurons of the dorsal root ganglion (DRG). Results from previous studies suggest that MrgprD participates in mechanical hyperalgesia and nerve injury-induced neuropathic pain. However, it remains elusive whether and how MrgprD is involved in inflammatory pain. Here, we used a mouse model of chronic inflammatory pain established by intraperitoneal administration of lipopolysaccharide (LPS). The LPS injection induced an evident peripheral neuroinflammation and mechanical hyperalgesia in the mice and increased MrgprD expression in the DRG. The LPS administration also augmented the proportion of MrgprD-expressing neurons in the lumbar 4 DRG. Behaviorally, the LPS-induced hypersensitivities to mechanical and cold stimuli, but not to a heat stimulus, were substantially attenuated in Mrgprd-knockout mice compared with wildtype littermates. Mrgprd deletion in DRGs suppressed the LPS-triggered activation of the NF-κB signaling pathway and attenuated LPS-induced up-regulation of pro-inflammatory factors. Moreover, ectopic overexpression of MrgprD in HEK293 cells stably expressing mouse toll-like receptor 4 (TLR4) markedly promoted the LPS-induced NF-κB activation and enhanced NF-κB's DNA-binding activity. Furthermore, MrgprD physically interacted with TGF-β-activated kinase 1 (TAK1) and I-kappa-B-kinase (IKK) complexes, but not with mitogen-activated protein kinases (MAPKs) in mouse DRGs. In macrophage-like RAW 264.7 cells, MrgprD also interacted with TAK1 and IKK complex, and the treatment of MrgprD agonist elicited the activation of NF-κB signaling, but not of mitogen-activated protein kinases (MAPKs) signaling pathway. Our findings indicate that MrgprD facilitates the development of LPS-triggered persistent inflammatory hyperalgesia by promoting canonical NF-κB activation, highlighting the important roles of MrgprD in NF-κB-mediated inflammation and chronic pain.
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http://dx.doi.org/10.1016/j.cellsig.2020.109813DOI Listing
December 2020

Beneficial effects of galanin system on diabetic peripheral neuropathic pain and its complications.

Peptides 2020 12 6;134:170404. Epub 2020 Sep 6.

Department of Physiology, School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China. Electronic address:

Diabetic peripheral neuropathic pain (DPNP) is a distal spontaneous pain, caused by lesion of sensory neurons and accompanied by depression and anxiety frequently, which reduce life quality of patients and increase society expenditure. To date, antidepressants, serotonin-noradrenaline reuptake inhibitors and anticonvulsants are addressed as first-line therapy to DPNP, alone or jointly. It is urgently necessary to develop novel agents to treat DPNP and its complications. Evidences indicate that neuropeptide galanin can regulate multiple physiologic and pathophysiological processes. Pain, depression and anxiety may upregulate galanin expression. In return, galanin can modulate depression, anxiety, pain threshold and pain behaviors. This article provides a new insight into regulative effects of galanin and its subtype receptors on antidepressant, antianxiety and against DPNP. Through activating GALR1, galanin reinforces depression-like and anxiogenic-like behaviors, but exerts antinociceptive roles. While via activating GALR2, galanin is referred to as anti-depressive and anti-anxiotropic compounds, and at low and high concentration facilitates and inhibits nociceptor activity, respectively. The mechanism of the galanin roles is relative to increase in K currents and decrease in Ca currents, as well as neurotrophic and neuroprotective roles. These data are helpful to develop novel drugs to treat DPNP and its complications.
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http://dx.doi.org/10.1016/j.peptides.2020.170404DOI Listing
December 2020

Molecular and Cytogenetic Characterization of a Wheat-Rye 7BS.7RL Translocation Line with Resistance to Stripe Rust, Powdery Mildew, and Fusarium Head Blight.

Phytopathology 2020 Oct 3;110(10):1713-1720. Epub 2020 Sep 3.

College of Agronomy, Sichuan Agricultural University, Wenjiang, Chengdu, Sichuan, 611130, China.

is used as a source of genes for disease resistance in wheat cultivation. In this study, a homozygous translocation line (RT14-245) that originated from a cross between a commercial wheat cultivar (Mianyang 11) and a local Chinese variety of rye (Baili was developed. Multicolor fluorescence in situ hybridization and PCR analysis demonstrated that the translocation chromosome was 7BS.7RL. Resistance analysis showed that RT14-245 was resistant to prevalent pathotypes of stripe rust and powdery mildew. RT14-245 also exhibited high resistance to Fusarium head blight, which was similar to the resistance exhibited by the wheat cultivar Sumai 3. The results indicated that RT14-245 simultaneously exhibited high levels of resistance against stripe rust, powdery mildew, and Fusarium head blight. These results indicate that chromosome arm 7RL in the translocation line RT14-245 is an excellent new resource for wheat breeding programs.
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http://dx.doi.org/10.1094/PHYTO-02-20-0061-RDOI Listing
October 2020

Antipruritic Effect of Ethyl Acetate Extract from in Mice with 2,4-Dinitrofluorobenzene-Induced Atopic Dermatitis.

Evid Based Complement Alternat Med 2020 6;2020:6981386. Epub 2020 May 6.

School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, 138 XianLin Road, Nanjing 210023, China.

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by intense pruritus and skin lesions. The exact cause of AD is not yet known and the available therapeutic strategies for AD are limited. is commonly used in traditional Chinese medicine as an herb for treating chronic itch. However, the mechanism underlying the antipruritic effects of is not well understood. In the present study, we investigated the antipruritic effect of locally administered ethyl acetate extract from (EAEFC) to 2,4-dinitrofluorobenzene- (DNFB-) induced AD in a mouse model. The scratching behavior, skin thickness, dermatitis score, weight, blood immunoglobulin E (IgE) level, and itch-related cytokine levels were subsequently monitored and evaluated. Results showed that EAEFC treatment attenuated the DNFB-induced AD-like symptoms by alleviating the skin lesions and decreasing the dermatitis score. Hematoxylin and eosin (H&E) and toluidine blue (TB) staining analyses demonstrated that EAEFC mitigated the DNFB-induced increase in skin thickness and prevented the infiltration of mast cells. Behavioral tests showed that EAEFC decreased the DNFB-induced acute and chronic scratching behaviors. Furthermore, EAEFC reduced the levels of itch-related cytokines, such as thymic stromal lymphopoietin (TSLP), interleukin- (IL-) 17, IL-33, and IL-31, and the DNFB-induced boost in serum IgE. Collectively, these results suggest that EAEFC is a potential therapeutic candidate for the treatment of chronic itch in AD.
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http://dx.doi.org/10.1155/2020/6981386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229549PMC
May 2020

Molecular dissection of Secale africanum chromosome 6R in wheat enabled localization of genes for resistance to powdery mildew and stripe rust.

BMC Plant Biol 2020 Mar 31;20(1):134. Epub 2020 Mar 31.

Center for Informational Biology, School of Life Science and Technology, University of Electronic and Technology of China, Chengdu, 611731, Sichuan, China.

Background: Introgression of chromatin from Secale species into common wheat has for decades been a successful strategy for controlling the wheat diseases. The wild Secale species, Secale africanum Stapf., is a valuable source for resistance to foliar disease of wheat. A wheat-S. africanum chromosome 6R substitution line displayed resistance to both powdery mildew and stripe rust at the adult-plant stage.

Results: Wheat-S. africanum chromosome 6R deletion and translocation lines were produced and identified by sequential non-denaturing fluorescence in situ hybridization (ND-FISH) using multiple Oligo-based probes. Different ND-FISH patterns were observed between S. cereale 6R and S. africanum 6R. With reference to the physical map of the draft genome sequence of rye inbred line Lo7, a comprehensive PCR marker analysis indicated that insertions and deletions had occurred by random exchange between chromosomes 6R and 6R. A survey of the wheat- S. africanum 6R lines for disease resistance indicated that a powdery mildew resistance gene(s) was present on the long arm of 6R at FL0.85-1.00, and that a stripe rust resistance gene(s) was located in the terminal region of 6RS at FL0.95-1.00. The wheat-S. africanum 6R introgression lines also displayed superior agronomic traits, indicating that the chromosome 6R may have little linkage drag in the wheat background.

Conclusions: The combination of molecular and cytogenetic methods allowed to precisely identify the chromosome rearrangements in wheat- S. africanum 6R substitution, deletion and translocation lines, and compare the structural difference between chromosomes 6R and 6R. The wheat- S. africanum 6R lines containing gene(s) for powdery mildew and stripe rust resistance could be used as novel germplasm for wheat breeding by chromosome engineering.
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http://dx.doi.org/10.1186/s12870-020-02351-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106737PMC
March 2020

The production of wheat - 1S chromosome substitution lines harboring alien novel high-molecular-weight glutenin subunits.

Genome 2020 Mar 17;63(3):155-167. Epub 2019 Dec 17.

State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China.

In our previous work, a novel high-molecular-weight glutenin subunit (HMW-GS) with an extremely large molecular weight from was identified that may contribute to excellent wheat () processing quality and increased dough strength, and we further generated HMW-GS homozygous lines by crossing. In this study, we crossed the HMW-GS homozygous line 66-17-52 with 'Chinese Spring' Ph1 mutant CS to induce chromosome recombination between wheat and . SDS-PAGE was used to identify 19 derived F lines with the HMW-GSs of . The results of non-denaturing fluorescence in situ hybridization (ND-FISH) indicated that lines 6-1 and 6-7 possessed a substitution of both 5D chromosomes by a pair of 1S chromosomes. Further verification by newly developed 1S-specific chromosome markers showed that these two lines amplified the expected fragment. Thus, it was concluded that lines 6-1 and 6-7 are 1S(5D) chromosome substitution lines. The 1S(5D) chromosome substitution lines, possessing alien subunits with satisfactory quality-associated structural features of large repetitive domains and increased number of subunits, may have great potential in strengthening the viscosity and elasticity of dough made from wheat flour. Therefore, these substitution lines can be used for wheat quality improvement and further production of 1S translocation lines.
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http://dx.doi.org/10.1139/gen-2019-0106DOI Listing
March 2020

Responses of the proteome in testis of mice exposed chronically to environmentally relevant concentrations of Microcystin-LR.

Ecotoxicol Environ Saf 2020 Jan 22;187:109824. Epub 2019 Oct 22.

Department of Physiology, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China. Electronic address:

Microcystin-LR (MC-LR), a widespread environmental contaminant, has been shown to have potent acute testicular toxicity. However, magnitudes of toxic effects, induced by MCs, depend on route and magnitude of exposure to the toxin. In the present study, male mice were orally exposed 1, 10 or 100 μg/L MC-LR for 90 or 180 days, and pathological approach and the isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics were employed with testes. Proteomics revealed that a number of differentially altered proteins may be involved in MC-LR-induced chronic testicular toxicity. The biological process analysis indicated the altered proteins played an important role in biological adhesion, cellular process, response to stimulus or rhythmic process. The cellular component analysis revealed that most of the proteins with altered expression associated with cell part, extracellular region, extracellular region part, membrane, membrane part, organelle or organelle part. The molecular function showed that these proteins were critical in molecular transducer activity. Integrity analyses provide first compelling evidence that MC-LR significantly cause dysfunction of blood-testis barrier (BTB) through affecting tight junctions and gap junctions. Moreover, phosphatidylinositol 3-kinase (PI3K)/AKT eventually contributed to injury result from chronic low-level MC-LR treatment. Identification of proteins in testis responsive to MC-LR provides insights into molecular mechanisms of chronic toxicity of MCs.
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http://dx.doi.org/10.1016/j.ecoenv.2019.109824DOI Listing
January 2020

Characteristics of compound 48/80-induced voltage-dependent currents in mouse mast cell tumor P815 cells.

Acta Biochim Biophys Sin (Shanghai) 2019 Oct 14. Epub 2019 Oct 14.

School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing 210000, China.

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http://dx.doi.org/10.1093/abbs/gmz108DOI Listing
October 2019

Circular RNA expression profiling in the nucleus accumbens: Effects of electroacupuncture treatment on morphine-induced conditioned place preference.

Addict Biol 2020 07 26;25(4):e12794. Epub 2019 Jun 26.

Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, China.

Electroacupuncture (EA) has been developed on the basis of traditional Chinese acupuncture. EA can suppress craving in opioid addicts and opioid-seeking responses in rodents. However, the molecular mechanism of EA on the rewarding properties of morphine and craving responses is not known. Here, we have applied a conditioned place preference paradigm in mice to measure morphine-induced rewarding effects along with EA treatment. Circular RNAs (circRNAs) can function as micro RNA (miRNA) sponges to effectively regulate gene expression levels. CircRNA profiling within the nucleus accumbens (NAc) was performed in EA-treated and sham-treated mice. Following RNAseq, data were analyzed by gene ontology (GO) and Kyoto Encyclopedia Genes and Genomes (KEGG) tools. We identified 112 significantly differentially expressed circRNAs, including 51 that were up-regulated and 61 that were down-regulated. Our bioinformatics analyses show that these differentially expressed circRNAs map into pathways that are mainly involved with renin secretion and the cGMP-PKG signaling. We further constructed a circRNA-miRNA network that predicts the potential roles of the differentially expressed circRNAs and the interaction of circRNAs with miRNAs. Our secondary sequencing and bioinformatics analysis in the NAc after EA treatment on morphine-induced CPP provides putative novel targets on molecular mechanisms involved in morphine reinforcement and possibly craving.
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http://dx.doi.org/10.1111/adb.12794DOI Listing
July 2020

Icariin attenuate microcystin-LR-induced gap junction injury in Sertoli cells through suppression of Akt pathways.

Environ Pollut 2019 Aug 26;251:328-337. Epub 2019 Apr 26.

School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China. Electronic address:

Microcystin-leucine-arginine (MC-LR) can cause male reproductive disorder. However, the underlying mechanism are not yet entirely elucidated. In this study, we aimed to investigated the effects of MC-LR on the integrity of blood-testis barrier (BTB) and the related molecular mechanisms. Both in vivo and in vitro experiments revealed that MC-LR caused disruption of BTB and gap junctions between Sertoli cells respectively, which was paralleled by the alteration of connexin43 (Cx43). Our data demonstrated that MC-LR decreased gap junction intercellular communication (GJIC) and impaired Cx43 expression by activating the phosphatidylinositol 3-kinase/Akt cascades. In addition, a possible protective effect of Icariin (ICA), a flavonoid isolated from Chinese medicinal herb, against MC-LR toxicity was investigated. The ICA prevented the degradation of GJIC and impairment of Cx43 induced by MC-LR via suppressing the Akt pathway. Together, our results confirmed that the expression of Cx43 induced by MC-LR was regulated in vivo and in vitro, which was involved in the destruction of BTB. Additionally, ICA seems to be able to mitigate the MC-LR toxic effects.
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http://dx.doi.org/10.1016/j.envpol.2019.04.114DOI Listing
August 2019

New ND-FISH-Positive Oligo Probes for Identifying Chromosomes in Wheat Backgrounds.

Int J Mol Sci 2019 Apr 25;20(8). Epub 2019 Apr 25.

Provincial Key Laboratory of Plant Breeding and Genetics, Sichuan Agricultural University, Wenjiang, Chengdu 611130, Sichuan, China.

has been widely used to improve wheat ( L.) cultivars. Non-denaturing fluorescence in situ hybridization (ND-FISH) technology using oligonucleotides (oligo) as probes provides a convenient and efficient way to identify alien chromosomes in wheat backgrounds. However, suitable ND-FISH-positive oligo probes for distinguishing chromosomes from wheat are lacking. Two oligo probes, Oligo-B11 and Oligo-pThp3.93, were designed according to the published ()-specific repetitive sequences. Both Oligo-B11 and Oligo-pThp3.93 can be used for ND-FISH analysis and can replace conventional GISH and FISH to discriminate some chromosomes of , , and in wheat backgrounds. The two oligo probes provide a convenient way for the utilization of germplasms in future wheat breeding programs.
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http://dx.doi.org/10.3390/ijms20082031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515231PMC
April 2019

Expression and localization of MrgprD in mouse intestinal tract.

Cell Tissue Res 2019 Aug 27;377(2):259-268. Epub 2019 Mar 27.

Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, 210023, Jiangsu, People's Republic of China.

MrgprD, a Mas-related G protein-coupled receptor, is initially identified in sensory neurons of mouse dorsal root ganglia (DRG) and has been suggested to participate in somatosensation. However, MrgprD has recently been found to be expressed outside the nervous system such as in aortic endothelia cells and neutrophils. In this study, we used immunohistochemistry to detect the expression and localization of MrgprD in mouse intestinal tract. The immunoreactivity (IR) of MrgprD was found in the smooth muscle layers of small intestine, colon and rectum. In addition, MrgprD IR was colocalized with F4/80-positive macrophages and CD3-positive T lymphocytes resident in the lamina propria of intestinal mucosa. MrgprD was also found to be expressed in primary peritoneal macrophages and splenic T lymphocytes. Furthermore, the presence of MrgprD mRNA and its protein was detected in murine macrophage-like RAW 264.7 and human T lymphocyte Jurkat cell lines. Our study shows, for the first time, the expression and localization of MrgprD in the intestinal tract and in macrophages and T lymphocytes, indicating the potential roles of MrgprD in intestinal mobility and immunity.
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http://dx.doi.org/10.1007/s00441-019-03017-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647478PMC
August 2019

The Polymorphisms of Oligonucleotide Probes in Wheat Cultivars Determined by ND-FISH.

Molecules 2019 Mar 21;24(6). Epub 2019 Mar 21.

Provincial Key Laboratory for Plant Genetics and Breeding, Wenjiang, Chengdu 611130, Sichuan, China.

Non-denaturing fluorescence in situ hybridization (ND-FISH) has been used to distinguish wheat chromosomes and to detect alien chromosomes in the wheat genome. In this study, five different oligonucleotide probes were used with ND-FISH to examine 21 wheat cultivars and lines. These oligonucleotide probes distinguished 42 wheat chromosomes and also detected rye chromatin in the wheat genome. Moreover, the signal patterns of the oligonucleotide probes Oligo-pTa535-1 and Oligo-pSc119.2-1 showed high polymorphism in the wheat chromosomes. A total of 17.6% of the A group chromosomes, 25.9% of the B group chromosomes and 8.9% of the D group chromosomes showed obvious mutations when they were compared to the standard ND-FISH signal patterns, and most of them were Oligo-pSc119.2-1 mutants. The results suggested that these polymorphisms could be induced by the crossing of wheat cultivars. The results provided more information for the further application of oligonucleotide probes and ND-FISH.
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http://dx.doi.org/10.3390/molecules24061126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471732PMC
March 2019

The genome-wide transcriptional consequences of the nullisomic-tetrasomic stocks for homoeologous group 7 in bread wheat.

BMC Genomics 2019 Jan 10;20(1):29. Epub 2019 Jan 10.

Key Laboratory of Wheat Biology & Genetic Improvement on North Yellow & Huai River Valley, Ministry of Agriculture, National Engineering Laboratory for Wheat & Maize, Institute of Crop Science, Shandong Academy of Agricultural Sciences (SAAS), #202, Road of Gongyebei, Jinan, 250100, China.

Background: Hexaploid bread wheat (Triticum aestivum L) arose by two polyploidisation events from three diploid species with homoeologous genomes. Nullisomic-tetrasomic (nulli-tetra or NT) lines are aneuploid wheat plants lacking two and adding two of six homoeologous chromosomes. These plants can grow normally, but with significantly morphological variations because the adding two chromosomes or the remaining four chromosomes compensate for those absent. Despite these interesting phenomena, detailed molecular mechanisms underlying dosage deletion and compensation in these useful genetic materials have not been determined.

Results: By sequencing the transcriptomes of leaves in two-week-old seedlings, we showed that the profiles of differentially expressed genes between NT stocks for homoeologous group 7 and the parent hexaploid Chinese Spring (CS) occurred throughout the whole genome with a subgenome and chromosome preference. The deletion effect of nulli-chromosomes was compensated partly by the tetra-chromosomes via the dose level of expressed genes, according to the types of homoeologous genes. The functions of differentially regulated genes primarily focused on carbon metabolic process, photosynthesis process, hormone metabolism, and responding to stimulus, and etc., which might be related to the defective phenotypes that included reductions in plant height, flag leaf length, spikelet number, and kernels per spike.

Conclusions: The perturbation of the expression levels of transcriptional genes among the NT stocks for homoeologous group 7 demonstrated the gene dosage effect of the subgenome at the genome-wide level. The gene dosage deletion and compensation can be used as a model to elucidate the functions of the subgenomes in modern polyploid plants.
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http://dx.doi.org/10.1186/s12864-018-5421-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327598PMC
January 2019

Brucine alleviates neuropathic pain in mice via reducing the current of the sodium channel.

J Ethnopharmacol 2019 Apr 30;233:56-63. Epub 2018 Dec 30.

School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, 138 Xianlin Rd, Nanjing, 210023 Jiangsu, China; Key Laboratory for Chinese Medicine of Prevention and Treatment in Neurological Diseases, Nanjing University of Chinese Medicine, 138 Xian in Rd, Nanjing, 210023 Jiangsu, China; State Key Laboratory Cultivation Base for TCM Quality and Efficacy, School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, China; Key Laboratory of Drug Target and Drug for Degenerative Disease of Jiangsu Province, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address:

Ethnopharmacological Relevance: Strychnos nux-vomica L. (Loganiaceae) is grown extensively in South Asian. The dried seed of this plant, nux vomica, has been clinically used in Chinese medicine for relieving rheumatic pain, reducing swelling and treating cancer. Brucine, the second abundant alkaloid constituent of nux vomica, shows excellent clinical therapeutic effect, especially in relieving pain, but mechanism of brucine in relieving pain is still unclear.

Aim Of The Study: Explore the analgesic effect of brucine, reveal the molecular mechanism of brucine analgesia.

Materials And Methods: Antinociceptive effects of brucine were assessed in acute and chronic pain mice model. Electrophysiological experiments were used to evaluate the effects of brucine on neuronal activity and sodium channel function.

Results: In acute pain models, brucine significantly inhibits response induced by nociceptive heat and mechanical stimulation. Furthermore, thermal hypersensitivity and mechanical allodynia were also alleviated by brucine treatment in a chronic constriction injury (CCI) mouse model. Sodium channel plays a crucial role in neuropathic pain. Electrophysiological results show that brucine inhibits the excitability of DRG neurons directly, the number of action potential (AP) was significantly reduced after brucine treatment, and this kind of inhibition is due to brucine inhibits both tetrodotoxin-sensitive (TTXs) and tetrodotoxin-resistant (TTXr) sodium channel.

Conclusions: Taken together, brucine is a novel drug candidate in treating acute and chronic pain diseases, which might be attributed to inhibition the excitability of sodium channel directly.
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http://dx.doi.org/10.1016/j.jep.2018.12.045DOI Listing
April 2019

Using the 6RL Minichromosome of Rye ( L.) to Create Wheat-Rye 6D/6RL Small Segment Translocation Lines with Powdery Mildew Resistance.

Int J Mol Sci 2018 Dec 7;19(12). Epub 2018 Dec 7.

College of Agronomy, Sichuan Agricultural University, Wenjiang, Chengdu 611130, China.

Long arms of rye ( L.) chromosome 6 (6RL) carry powdery mildew resistance genes. However, these sources of resistance have not yet been successfully used in commercial wheat cultivars. The development of small segment translocation chromosomes carrying resistance may result in lines carrying the 6R chromosome becoming more commercially acceptable. However, no wheat-rye 6RL small segment translocation line with powdery mildew resistance has been reported. In this study, a wheat-rye 6RL minichromosome addition line with powdery mildew resistance was identified, and this minichromosome was derived from the segment between L2.5 and L2.8 of the 6RL chromosome arm. Following irradiation, the 6RL minichromosome divided into two smaller segments, named 6RL and 6RL, and these fragments participated in the formation of wheat-rye small segment translocation chromosomes 6DS/6RL and 6DL/6RL, respectively. The powdery mildew resistance gene was found to be located on the 6RL segment. Sixteen 6RL-specific markers were developed, and their products were cloned and sequenced. Nucleotide BLAST searches indicated that 14 of the 16 sequences had 91⁻100% similarity with nine scaffolds derived from 6R chromosome of L. Lo7. The small segment translocation chromosome 6DL/6RL makes the practical utilization in agriculture of powdery mildew resistance gene on 6RL more likely. The nine scaffolds are useful for further studying the structure and function of this small segment.
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http://dx.doi.org/10.3390/ijms19123933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320790PMC
December 2018

Sex Associated Differential Expressions of the Alternatively Spliced Variants mRNA of OPRM1 in Brain Regions of C57BL/6 Mouse.

Cell Physiol Biochem 2018 25;50(4):1441-1459. Epub 2018 Oct 25.

Pharmaceutical College, Nanjing University of Chinese Medicine, Jiangsu, China.

Background/aims: Opiates are potent analgesics but their clinical use is limited by sex-associated side effects, such as drug tolerance, opioid-induced hyperalgesia and withdrawal reaction. OPRM1, as the main receptor of opioids, plays an important role in the pharmacological process of opioids in rodents and human. We have previously investigated OPRM1, the μ opioid receptor gene, which have dozens of alternatively spliced variants probably correlating with opioid-induced effects in brain regions of four inbred mouse strains and demonstrated the strain-specific expressions of these splice variants. Also, within a strain, the regional expression patterns of some of the variants were similar while others were opposite. Thus, we are aiming to seek out the relationship between sex differences and these alternatively spliced variants.

Methods: The present studies follow a SYBR green quantitative PCR (qPCR) which we had used before to examine the expression of OPRM1 splice variant mRNAs in selected brain regions of male and female C57BL/6 mice. Sex-associated differences in baseline latency, opioid-induced tolerance, analgesia and addiction were examined and determined by Tail-flick test, jumps and statistical analysis.

Results: The mRNA levels of opioid receptor gene splice variants in male and female mice showed significant differences among the brain regions, implying region-specific alternative splicing of the OPRM1 gene, which was consistent with our previous study. More importantly, the complete mRNA expression profiles of the OPRM1 splice variants was also gender-specific, suggesting a sexual influence on OPRM1 alternative splicing.

Conclusion: In brief, we put forward that the distinctions among baseline latency, opioid-induced tolerance, analgesia and physical dependence in male and female mice might correlate with sex associated differential expressions of OPRM1 gene.
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http://dx.doi.org/10.1159/000494644DOI Listing
November 2018

Physical location of tandem repeats in the wheat genome and application for chromosome identification.

Planta 2019 Mar 24;249(3):663-675. Epub 2018 Oct 24.

School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, 610054, China.

Main Conclusion: A general distribution of tandem repeats (TRs) in the wheat genome was predicted and a new web page combined with fluorescence in situ hybridization experiments, and the newly developed Oligo probes will improve the resolution for wheat chromosome identification. Comprehensive sequence analysis of tandem repeats (TR) in the wheat reference genome permits discovery and application of TRs for chromosome identification. Genome-wide localization of TRs was identified in the reference sequences of Chinese Spring using Tandem Repeat Finder (TRF). A database of repeats unit size, array number, and physical coverage length of TRs in the wheat genome was built. The distribution of TRs occupied 3-5% of the wheat chromosomes, with non-random dispersal across the A, B, and D genomes. Three classes of TRs surrounding the predicted genes were compared. An optimized computer-assisted website page B2DSC was constructed for the general distribution and chromosomally enriched zones of TR sequences to be displayed graphically. The physical distribution of predicted TRs in the wheat genome by B2DSC matched well with the corresponding hybridization signals obtained with fluorescence in situ hybridization (FISH). We developed 20 oligonucleotide probes representing 20-60 bp lengths of high copy number of TRs and verified by FISH. An integrated physical map of TR-Oligo probes for wheat chromosome identification was constructed. Our results suggest that the combination of both molecular cytogenetics and genomic research will significantly benefit wheat breeding through chromosome manipulation and engineering.
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http://dx.doi.org/10.1007/s00425-018-3033-4DOI Listing
March 2019
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